The ability to manipulate gene expression is a fundamental tool essential for molecular studies. In model organisms, methods and tools to delete or overexpress genes have provided the means to study and characterize the molecular basis of complex biological phenomenon. Recent advances in genome biology and the discovery that RNA interference operates in mammalian cells now provide a foundation for similar studies in mammalian cells. Indeed, nearly every molecular biologically based project now requires the use of RNAi and expression clones. Over the past several years, investigators in this P01 have developed comprehensive tools to manipulate gene expression in mammalian cells. In addition, we have developed a facility that has the equipment and expertise to perform high throughput RNAi and expression screens. Based on these advances, we have created a gene function manipulation core to support the projects in this P01. Specifically, this core will provide lentivirally delivered short hairpin RNA (shRNA) reagents and cDNA clones to program investigators. In addition, this facility will work with P01 investigators to perform shRNA and overexpression screens to elucidate components of the pathways perturbed by viral oncoproteins. Although such reagents can be developed on a gene-by-gene basis, this core facility will provide the reagents and means to manipulate gene expression in a comprehensive manner that is both efficient and cost effective. The access and use of this facility will thus accelerate progress for each of the projects that comprise this program.